Background: This R01 is in response to PAR-13-130: Understanding and Promoting Health Literacy (R01). Health literacy is the degree to which an individual can obtain, process, and understand basic health information, which includes the ability to understand written questionnaires. Almost none of the survey instruments being used across the country has been validated for use with people who have low health literacy. This fundamental cross-cutting weakness in survey methods undermines the accuracy of a broad swath of data collected in research and clinical care. Written questionnaires are omnipresent in healthcare, including patient demographic forms, symptom assessment tools, and patient-reported outcome questionnaires. The NIH has invested heavily in the creation of the NIH Patient-Reported Outcomes Measurement Information System (PROMIS), which has significantly advanced health measurement. But PROMIS, like almost all survey instruments, has not been validated for use by people with low health literacy and it exists in a written format that may be inaccessible to individuals with low literacy. Aims: We will remove health literacy barriers to accurate survey research by: 1) evaluating differences in psychometric properties by health literacy of PROMIS questionnaires as well as other commonly used surveys; 2) identifying and characterizing survey items that do not work properly for people with low health literacy; and, 3) creating a guide for survey item development and evaluation for different modes of test administration that are most appropriate for people who have low health literacy. Methods: We will recruit a large sample of participants across two primary care networks at Northwestern Universtiy and Boston University Medical Center. The sample will be evenly balanced across English versus Spanish language and adequate versus low health literacy. These assessments will be given at multiple time points as part of a longitudinal study. We will use state-of-the-art psychometric methods to determine differences among participants with low versus adequate health literacy, and whether these differences can be overcome by alternative modes of survey administration. Impact: We will identify survey item characteristics that are associated with differential item functioning by health literacy for different modes of test administration. Based on our analyses, we will create a guide for survey item development and evaluation. This will lead to assessments in healthcare that are more accessible for people with low health literacy and more accurate. This project has broad relevance insofar as many widely-used health questionnaires have not been validated for use with people who have low health literacy. We will present a generalizable approach that can rapidly influence the mode of data collection from patients. We will also present modes of data analyses oriented toward understanding health-literacy, which is a critical component of survey validation activities.